Kronos Early Estrogen Prevention Study (KEEPS)
Information source: Kronos Longevity Research Institute
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Menopause; Arteriosclerosis
Intervention: Conjugated equine estrogens 0.45 mg/day (Drug); Transdermal estradiol, 50 mcg/day (Drug); Micronized progesterone, 200 mg/day x 12 d/month (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Kronos Longevity Research Institute Official(s) and/or principal investigator(s):
S Mitchell Harman, MD, PhD, Study Director, Affiliation: Kronos Longevity Research Institute
Frederick Naftolin, MD, PhD, Study Director, Affiliation: Kronos Longevity Research Institute
Michael Mendelsohn, MD, Principal Investigator, Affiliation: Tufts Medical Center
Howard Hodis, MD, Principal Investigator, Affiliation: University of Southern California
Matthew Budoff, MD, Principal Investigator, Affiliation: University of California, Los Angeles
Sanjay Asthana, MD, Principal Investigator, Affiliation: University of Wisconsin, Madison
Dennis M Black, PhD, Principal Investigator, Affiliation: University of California, San Francisco
Overall contact:
Patricia Crenshaw, BA, Phone: (866) 878-1221, Email: info@kronosinstitute.org
Summary
The study will examine the effects of estrogen and progesterone on the development of
atherosclerosis in menopausal women when hormone treatment is initiated within 3 years of
the menopausal transition.
Clinical Details
Official title: Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women
Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Rate of change of carotid intimal medial thickness by ultrasound
Secondary outcome: Change in coronary calcium score by X-ray tomographyPlasma lipid profiles Blood clotting factors Serum inflammatory factors Hormone levels Cognitive and Affective scores on standard psychometric tests Quality of life
Detailed description:
The KEEPS is designed to explore the hypothesis that early initiation of hormone therapy, in
women who are at the inception of their menopause, will decrease the rate of accumulation of
atherosclerotic plaque, indicating a likely delay in the onset of clinical cardiovascular
disease. The study is designed as a multicenter, 4 year randomized clinical trial. It will
evaluate the effectiveness of of 0. 45 mg/day of oral conjugated equine estrogens or 50
mcg/day of transdermal estradiol via skin patch changed weekly (each in combination with
cyclic oral, micronized progesterone, 200 mg daily for 12 days per month), versus placebo in
preventing progression of carotid intimal medial thickness by sonogram and the accrual of
coronary calcium in women aged 42-58 who are within 36 months of their final menstrual period
at initiation of treatment. A number of secondary endpoints including biochemical and genetic
risk factors for cardiovascular and thrombotic disease, and effects on cognition will also be
studied. The study will enroll a total of 720 women in 2005-6, with an anticipated completion
of the trial in 2010.
Eligibility
Minimum age: 42 Years.
Maximum age: 58 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- menses absent for at least 6 months and no more than 36 months
- good general health
- plasma FSH level greater than or equal to 35 mIU/ml
- estradiol levels < 40 pg/ml
- normal mammogram within 1 year of randomization
Exclusion Criteria:
- use of hormone replacement or supplement within 3 months of randomization
- endometrial thickness >5 mm by vaginal ultrasound
- in utero exposure to diethylstilbestrol (DES)
- current smoking > 10 cigarettes/day
- obesity-body mass index > 35
- history of clinical cardiovascular disease
- history of cerebrovascular disease
- history of thromboembolic disease
- coronary calcium score ≥ 50 units
- dyslipidemia-LDL cholesterol >190 mg/dl
- hypertriglyceridemia-triglycerides >400 mg/dl
- lipid lowering medication (statin, fibrate,or > 500 mg/day of niacin)
- nut allergy (Prometrium includes peanut oil)
- uncontrolled hypertension-systolic BP >150 and/or diastolic BP > 95
- hysterectomy
- history of, or prevalent, chronic diseases including any cancer (other than basal cell
skin cancers), renal failure, cirrhosis, diabetes mellitus, and endocrinopathies other
than adequately treated thyroid disease
- known HIV infection and/or medications for HIV infection
- results of any safety laboratory test chemistries, (TSH, CBC, U/A) more than 20%
abnormal
Locations and Contacts
Patricia Crenshaw, BA, Phone: (866) 878-1221, Email: info@kronosinstitute.org
University of California, San Francisco, San Francisco, California 94115, United States; Recruiting
Nancy Jancar, RN, Phone: 415-353-4300, Email: keepstudy@ucsfmedctr.org
Marcelle I Cedars, MD, Principal Investigator
Yale University, New Haven, Connecticut 06520, United States; Recruiting
Diane Wall, RN, Phone: 203-737-5169, Email: diane.wall@yale.edu
Hugh S Taylor, MD, Principal Investigator
Brigham and Women's Hospital, Boston, Massachusetts 02215, United States; Recruiting
Kathryn Kalan, RN, Phone: 617-732-9871, Email: kkalan@partners.org
JoAnn E Manson, MD, DrPH, Principal Investigator
Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Teresa Zais, RN, Phone: 507-538-0848, Email: zais.teresa@mayo.edu
Virginia E Miller, PhD, Principal Investigator
Columbia Presbyterian Hospital, New York, New York 10032, United States; Recruiting
Amber Ahmad, MPH, Phone: 212-305-9672, Email: aa2430@columbia.edu
Luz Sanabria, Phone: 212-305-9672, Email: ls2328@columbia.edu
Roger Lobo, MD, Principal Investigator
Albert Einstein College of Medicine, Bronx, New York 10461, United States; Recruiting
Barbara Isaac, RN, Phone: 718-430-8656, Email: bisaac@aecom.yu.edu
Nanette F Santoro, MD, Principal Investigator
University of Utah, Salt Lake City, Utah 84108, United States; Recruiting
Stacey Larrinaga-Shum, Phone: 801-581-3888, Ext: 249, Email: Stacey.Larrinaga-shum@hsc.utah.edu
Eliot Brinton, MD, Principal Investigator
University of Washington/VA Puget Sound, HCS, Seattle/Tacoma, Washington 98493, United States; Recruiting
Colleen Carney, RN, Phone: 253-583-2040, Email: tiscolleen@yahoo.com
Suzanne Barsness, RN, Phone: 206-543-3897, Email: barsness@u.washington.edu
George R Merriam, MD, Principal Investigator
Additional Information
Information on hormone treatment and KEEPS rationale Information on sponsoring institution
Related publications: Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the Estrogen Controversy Over? Deconstructing the Women's Health Initiative Study: A Critical Evaluation of the Evidence. Ann N Y Acad Sci. 2005 Jun;1052:43-56. Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric. 2005 Mar;8(1):3-12. Harman SM, Brinton EA, Clarkson T, Heward CB, Hecht HS, Karas RH, Judelson DR, Naftolin F. Is the WHI relevant to HRT started in the perimenopause? Endocrine. 2004 Aug;24(3):195-202.
Starting date: September 2005
Ending date: June 2010
Last updated: May 3, 2006
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